目的:重复施用钆基造影剂(GBCA)后,中枢神经系统和周围神经系统中的钆滞留与脊髓病的主要表现和进行性神经系统症状之间的关系仍不清楚。我们研究了重复施用GBCAs对中枢神经系统和周围神经系统中钆滞留和感觉的影响,认知,和运动影响。
方法:将48只6周龄的雄性Wistar大鼠随机分为4个实验组(每组12只):加二酰胺组(线性和非离子GBCA),gadopentetate二甲葡胺组(线性和离子GBCA),gadoterate葡甲胺基团(大环和离子GBCA),对照组(0.9%生理盐水)。使用9.4TMRI扫描大鼠的大脑。进行感觉行为测试以评估GBCA对疼痛敏感性功能的影响。钆在大脑中沉积,脊髓,用电感耦合等离子体质谱法测定周围神经。采用透射电镜观察钆在脊髓中沉积后的微观分布。通过H&E染色分析脊髓的组织病理学特征,尼氏染色,胶质纤维酸性蛋白染色,和施用GBCA后的神经元特异性烯醇化酶染色。
结果:所有GBCA都导致钆沉积在中枢神经和周围神经组织中,在坐骨神经组织中沉积最高(平均,62.86[SD,12.56]nmol/g)。肌肉力量下降,空间认知功能受损,暴露于gadodiamide后观察到对热和机械刺激的疼痛过敏。在脊髓,透射电子显微镜发现,the沉积区域具有类似于“海胆”的球形结构,主要位于血管基底膜附近。
结论:多次注射GBCA会导致钆在大脑中沉积,脊髓,和周围神经,尤其是在gadodiamide组的脊髓中。加多二胺导致疼痛过敏,肌肉力量和认知能力下降。对于对疼痛过敏并需要多次MRI检查的患者,我们建议使用大环GBCA和尽可能低的剂量。
OBJECTIVE: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications.
METHODS: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs.
RESULTS: All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to \"sea urchins\" and was mainly located near the vascular basement membrane.
CONCLUSIONS: Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.